Efeito da suplementação da dieta com ácido fólico na colestase obstrutiva: estudo experimental em ratos jovens

Pós-graduação em Pediatria - FMB

Efeito da vitamina E-TPGS hidromiscível sobre as alterações nutricionais e a lesão hepática na colestase crônica

Pós-graduação em Pediatria - FMB

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents

OBJETIVOAnalisar os efeitos de 20 semanas de treinamento concorrente sobre as variáveis de composição corporal, perfil lipídico e diagnóstico da esteatose hepática em adolescentes obesos.MÉTODOSRealizou-se um ensaio clínico aberto com 34 adolescentes obesos com idades entre 12 e 15 anos. Foram analisados gordura corporal total e de tronco, colesterol total e suas frações (HDL, LDL e VLDL) e triglicérides, sendo realizado exame de ultrassonografia de abdome superior para diagnosticar esteatose hepática. Os participantes foram submetidos ao treinamento concorrente (associação de treino com pesos e exercício aeróbio) três vezes por semana, com duração de uma hora-aula durante 20 semanas. Para o tratamento estatístico, foram realizados o teste t de Student pareado e a análise de frequência, a fim de verificar as reduções relativa e absoluta do diagnóstico da esteatose hepática, adotando-se p<0,05.RESULTADOSOs adolescentes estudados apresentaram melhoras significativas da composição corporal, com diminuição do percentual de gordura total, da massa gorda total, da gordura de tronco e do aumento da massa magra, além de redução do tamanho dos lóbulos do fígado, dos índices de prevalência da esteatose hepática, do colesterol total e LDL-colesterol.CONCLUSÕESO treinamento concorrente foi efetivo por promover melhorias significativas de variáveis da composição corporal e do perfil lipídico, além de reduzir a prevalência da esteatose hepática.

Effects of Thermal Stress on Hepatic Melanomacrophages of Eupemphix nattereri (Anura)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Embolization of splenorenal shunt associated to portal vein thrombosis and hepatic encephalopathy

Hepatic encephalopathy (HE) is a cognitive disturbance characterized by neuropsychiatric alterations. It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts. The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration. Therefore, the embolization of these shunts has been performed to control HE manifestations, but the presence of portal vein thrombosis is considered a contraindication. In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt. Case report: a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma, even without precipitant factors. She had a wide portosystemic shunt and also portal vein thrombosis. The abdominal angiography confirmed the splenorenal shunt and showed other shunts. The larger shunt was embolized through placement of microcoils, and the patient had no recurrence of overt HE. There was a little increase of esophageal and gastric varices, but no endoscopic treatment was needed. Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients, portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization. However, in particular cases with many shunts and severe HE, we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery. In conclusion, we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis. As the patient had other shunts, she was successfully treated by embolization of the larger shunt. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Sex hormones change visceral pigmentation in Eupemphix nattereri (Anura): effects in testicular melanocytes and hepatic melanomacrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gastric and small intestinal lesions after partial stomach resection with Billroth II or Roux-en-Y reconstruction in the rat

The evolution and phenotypic expression of mucosal lesions of the gastric stump were investigated in male rats submitted to gastric resection with reconstruction by the Billroth II technique (BII with biliopancreatic reflux, BPR) or by the Roux-en-Y procedure (without BPR). Animals were studied at 24, 36, 54 and 64 weeks after surgery and the phenotypic expression of lesions analysed using routine hematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff (GOS) and sialidase GOS reactions). BPR was found to be responsible for the formation of adenomatous hyperplasia (AH), increasing in incidence and size with time, since the Roux-en-Y procedure failed to induce the gastric stump lesions observed after BII reconstruction. AHs always occurred in the transition of the gastrojejunal junction, a site offering special conditions for BPR influence, and were classified as gastric (G), intestinal (I) and G+I types according to their phenotypic expression. No pure I type AH was diagnosed at any time point. The G and G+I types developed at approximately equal incidences (i.e., G type 7/17, G+I type 10/17 at the 64th week). It was suggested that both gastric and intestinal mucosal elements were stimulated to proliferate by BPR, with the gastric mucosa tending to demonstrate AH. Intestinal type components of AH were found adjacent to the jejunum and not at the stomach margin, indicating an origin from intestinal mucosa. No metaplasia of the gastric mucosa was observed in any animal after partial gastric resection. In 101 rats submitted to the BII procedure, 5 mucinous adenocarcinomas were eventually diagnosed, mostly located in the subserosa of the gastrojejunal junction. All carcinomas expressed the phenotype of cells of the small intestine. Evidence of malignant transformation within the gastric components of AH was not observed even at the 64th week. In conclusion, all lesions induced by BPR in the rat remnant stomach are benign, and the few true cancers that arise in association are derived from the small intestine.

E2 potentializes benzo(a)pyrene-induced hepatic cytochrome P450 enzyme activities in Nile tilapia at high concentrations

In the aquatic environment, biotransformation enzymes are established biomarkers for assessing PAH exposure in fish, but little is known about the effect of 17β-estradiol (E2) on these enzymes during exposure to benzo(a)pyrene (BaP). In this study, Nile tilapia (Oreochromis niloticus) were exposed for 3, 5, and 10 days to BaP (300 μg L(-1)) and E2 (5 μg L(-1)). These substances were applied isolated or mixed. In the mixture experiment, fish were analyzed pre- and postexposure in order to better understand whether preexposure to the hormone masks the responses activated by PAH or vice versa. Phase I enzymes ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-depenthylase (PROD), and benzyloxyresorufin-O-debenzylase (BROD) activities as well as the phase II enzyme glutathione S-transferase (GST) were analyzed. Isolated E2 treatment decreased EROD activity after 3 days, but this enzyme activity returned to control values after 5 and 10 days of exposure. Isolated BaP treatment significantly induced EROD activity after 3 and 5 days, and the activity returned to control levels after ten exposure days. Combined treatment (E2 + Bap) significantly increased EROD activity, both in the pre- and postexposure. This increase was even higher than in the isolated BaP treatment, suggesting a synergism between these two compounds. When E2 and BaP were used singly, they did not change BROD and PROD activities. However, combined treatment (E2 + Bap) significantly increased PROD activity. Isolated BaP treatment increased GST activity after 10 days. However, this response was not observed in the mixture treatment, suggesting that E2 suppressed the GST induction modulated by BaP. The results put together indicated that E2 altered the biotransformation pathway regarding enzymes activated by BaP in Nile tilapia.

Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway.

Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocaecal resection for crohn's disease: results from the MULTIPER database

Both adalimumab [ADA] and infliximab [IFX] seem to be effective in the prevention of early postoperative endoscopic recurrence [EPER] after ileocaecal resection in Crohn's disease [CD] patients. There is lack of data with direct comparison between the two agents in the postoperative scenario. The aim of this study was to compare the rates of EPER in patients treated with ADA and IFX after ileocaecal resection for CD. This was a multicentre retrospective analysis of EPER rates in CD patients after ileocaecal resections, from seven referral centres in three countries. Endoscopic recurrence was defined as Rutgeerts' score ≥ i2. The patients were allocated according to treatment to two groups: ADA or IFX. The EPER rates were compared between the two treatment groups. Among the 168 patients included in the database, 96 received anti-tumour necrosis factor [TNF] agents after resection [37 in the ADA and 59 in the IFX groups] and were included in this comparative study. The groups were comparable in all baseline characteristics, mainly age, gender, previous resections, perianal CD, and mono or combination therapy. EPER was identified in 9/37 [24.32%] in the ADA group vs 16/59 [27.12%] in the IFX group [p = 0.815]. In this retrospective direct comparison between ADA and IFX therapy after ileocaecal resection, there was no significant difference between the two anti-TNF agents in terms of EPER rates. However, prospective randomised studies are needed to confirm these data and better define the role of each agent in the prevention of EPER.

Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state

To maintain euglycemia in healthy organisms, hepatic glucose production is increased during fasting and decreased during the postprandial period. This whole process is supported by insulin levels. These responses are associated with the insulin signaling pathway and the reduction in the activity of key gluconeogenic enzymes, resulting in a decrease of hepatic glucose production. On the other hand, defects in the liver insulin signaling pathway might promote inadequate suppression of gluconeogenesis, leading to hyperglycemia during fasting and after meals. The hepatocyte nuclear factor 4, the transcription cofactor PGC1-α, and the transcription factor Foxo1 have fundamental roles in regulating gluconeogenesis. The loss of insulin action is associated with the production of pro-inflammatory biomolecules in obesity conditions. Among the molecular mechanisms involved, we emphasize in this review the participation of TRB3 protein (a mammalian homolog of Drosophila tribbles), which is able to inhibit Akt activity and, thereby, maintain Foxo1 activity in the nucleus of hepatocytes, inducing hyperglycemia. In contrast, physical exercise has been shown as an important tool to reduce insulin resistance in the liver by reducing the inflammatory process, including the inhibition of TRB3 and, therefore, suppressing gluconeogenesis. The understanding of these new mechanisms by which physical exercise regulates glucose homeostasis has critical importance for the understanding and prevention of diabetes.